Long-term effects of adolescent sport experience, DRD2 and COMT genes, and their interaction on sport participation in adulthood.

BACKGROUND: The present study investigated the joint impact of adolescent sport experience and dopamine-related genes (i.e., DRD2 and COMT genes) on sport participation in adulthood. METHODS: Using the National Longitudinal Study of Adolescent Health (Add Health) data, the hierarchical multivariable logistic regression models for predicting sport participation in wave 3 (around 20 years of age) and wave 4 (around 30 years of age) were conducted separately by gender (male and female) and gene (DRD2 and COMT genes). RESULTS: Adolescent sport experience significantly interacted with the number of DRD2 A1 alleles and COMT Met alleles in affecting wave 3 sport participation among male adults. The interaction between adolescent sport experience and DRD2 gene significantly affected wave 4 sport participation in opposite direction to that affected wave 3 sport participation among male participants. Among female participants, there were no significant interaction effects between dopamine-related genes and adolescent sport experience on sport participation in both wave 3 and 4. CONCLUSIONS: Since adult sport participation is most likely to be influenced by the joint impact of environmental and genetic factors, it is important to consider gene-by-environment interactions when designing policies or programs to promote adult sport participation.

The effects of dopamine receptor genes on the trajectories of sport participation from adolescence through young adulthood.

Background: Although previous studies suggest that dopamine receptor genes partially affect physical activity-related behaviours, all of these studies were cross-sectional studies that examined the effects of dopamine receptor genes on physical activity-related behaviours at some point in time. Therefore, the nature and extent of this relationship across the lifespan are even more uncertain.Aim: The purpose of this study is to examine the effects of dopamine receptor genes (i.e. DRD2, DRD4 and DRD5) on sport participation trajectories from adolescence to young adulthood.Subjects and methods: This study used the National Longitudinal Study of Adolescent Health data (wave 1-4). Group-based trajectory modelling was used to investigate the effect of dopamine receptor genes on the probability of being in each sport participation trajectory group.Results: A three-group model was the best fitting model for men whereas a two-group model was the best fitting model for women. The more participants possess the A1 allele of the DRD2, the less likely they are to be in the "high-decreasing group" rather than the "low-stable group" in both men and women. In male participants, the more participants carry the A1 allele of the DRD2, the more likely they are to be in the "high-stable group" rather than the "high-decreasing group" (coefficient = 0.206, p<.05).Conclusions: These results can contribute to the literature by providing important information on the effects of dopamine receptor genes on sport participation trajectories from adolescence through young adulthood.

Differential expression of genes in the subgranular zone and granular cell layer of the hippocampus after running.

PURPOSE: Despite numerous studies, the mechanisms underlying the effects of exercise on brain function are not yet fully understood. Adult hippocampal neurogenesis is one of the most well-known effects of exercise on the brain, but its physiological roles during exercise are still ambiguous, mostly due to the difference in the structure and composition of each part of the hippocampus. METHODS: In this study, we analyzed exercise-induced changes in gene expression in the subgranular zone (SGZ) and granular cell layer (GCL) of the hippocampus. RESULTS: Surprisingly, only about 10% of changes were common to both areas. Tollip expression, which is altered in the SGZ and in Engrailed-2 mutant mice following exercise, did not change in the GCL. Tollip levels were not changed in the whole hippocampus after two weeks of treadmill exercise, but immunofluorescence analysis showed that Tollip and Ki-67 co-localize in the hippocampal dentate gyrus . Through siRNA knockdown experiments, we found that levels of DCX and cellular survival rates were decreased in Tollip-deficient Neuro2A cells. CONCLUSION: Taken together, these results suggest a role for Tollip in mediating the beneficial effects of exercise, probably affecting cellular health in the SGZ of the hippocampus.

Apolipoprotein a1 increases mitochondrial biogenesis through AMP-activated protein kinase.

Apolipoprotein a1, which is a major lipoprotein component of high-density lipoprotein (HDL), was reported to decrease plasma glucose in type 2 diabetes. Although recent studies also have shown that apolipoprotein a1 is involved in triglyceride (TG) metabolism, the mechanisms by which apolipoprotein a1 modulates TG levels remain largely unexplored. Here we demonstrated that apolipoprotein a1 increased mitochondrial DNA and mitochondria contents through sustained AMPK activation in myotubes. This resulted in enhanced fatty acid oxidation and attenuation of free fatty acid-induced insulin resistance features in skeletal muscle. The increment of mitochondria was mediated through induction of transcription factors, such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and nuclear transcription factor 1 (NRF-1). The inhibition of AMPK by a pharmacological agent inhibited the induction of mitochondrial biogenesis. Increase of AMPK phosphorylation by apolipoprotein a1 occurs through activation of upstream kinase LKB1. Finally, we confirmed that scavenger receptor Class B, type 1 (SR-B1) is an important receptor for apolipoprotein a1 in stimulating AMPK pathway and mitochondrial biogenesis. Our study suggests that apolipoprotein a1 can alleviate obesity related metabolic disease by inducing AMPK dependent mitochondrial biogenesis.

Emodin regulates glucose utilization by activating AMP-activated protein kinase.

AMP-activated protein kinase has been described as a key signaling protein that can regulate energy homeostasis. Here, we aimed to characterize novel AMP-activated kinase (AMPK)-activating compounds that have a much lower effective concentration than metformin. As a result, emodin, a natural anthraquinone derivative, was shown to stimulate AMPK activity in skeletal muscle and liver cells. Emodin enhanced GLUT4 translocation and [(14)C]glucose uptake into the myotube in an AMPK-dependent manner. Also, emodin inhibited glucose production by suppressing the expression of key gluconeogenic genes, such as phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, in hepatocytes. Furthermore, we found that emodin can activate AMPK by inhibiting mitochondrial respiratory complex I activity, leading to increased reactive oxygen species and Ca(2+)/calmodulin-dependent protein kinase kinase activity. Finally, we confirmed that a single dose administration of emodin significantly decreased the fasting plasma glucose levels and improved glucose tolerance in C57Bl/6J mice. Increased insulin sensitivity was also confirmed after daily injection of emodin for 8 days using an insulin tolerance test and insulin-stimulated PI3K phosphorylation in wild type and high fat diet-induced diabetic mouse models. Our study suggests that emodin regulates glucose homeostasis in vivo by AMPK activation and that this may represent a novel therapeutic principle in the treatment of type 2 diabetic models.